title: Restoration of growth arrest by p16INK4, p21WAF1, pRB, and p53 is dependent on the integrity of the endogenous cell-cycle control pathways in human glioblastoma cell lines.
abstract: The aim of this study was to demonstrate that the induction of growth arrest in human glioblastoma multiforme (GBM) cell lines by retrovirus-mediated transduction of growth control genes was dependent upon the integrity of specific endogenous control pathways. We assessed the status of the endogenous p16INK4A, p21CIP1, pRb, or p53 genes in eight GBM lines. As expected, we found varied combinations of gene defects. The outcome of transducing five of these cell lines with p16INK4A, p21CIP1, pRb, or p53 genes was not entirely predictable. The growth-inhibitory effects mediated by the transfer of the gene encoding p16 was dependent on the presence of the pRb protein, but was independent of p53 status. p21, a broadly active CDK inhibitor and a strong inducer of growth arrest, was not a universal growth suppressor in the group of glioblastoma cell lines analyzed. The suppression of GBM cell proliferation by viruses encoding pRb or p53 was generally predictable and appeared to be independent of the status of either p16 or p21. Suppression of cell growth was assessed by a colony formation assay, by observance of alterations in morphology, and by cell viability staining for trypan blue exclusion. Our findings suggest that to accomplish the suppression of GBM cell proliferation by the transduction of these cell-cycle control genes, the status of endogenous cell-cycle control genes must be taken into account.
authors.affiliation: Cancer Center, University of California, San Diego 92093-0063, USA.
authors.forename: E
authors.initials: E
authors.lastname: Costanzi-Strauss
authors.forename: B E
authors.initials: BE
authors.lastname: Strauss
authors.forename: R K
authors.initials: RK
authors.lastname: Naviaux
authors.forename: M
authors.initials: M
authors.lastname: Haas
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002455:Cell Division; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005909:Glioblastoma; D006801:Humans; D007700:Kinetics; D011994:Recombinant Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000378:metabolism*; D012190:Retroviridae; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: C493956:CDKN1A protein, human; C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins